Content of myeloid-derived suppressor cells in autoimmune diseases in children
- Authors: Radygina T.V.1, Kuptsova D.G.1, Petrichuk S.V.1, Potapov A.S.1,2, Murashkin N.N.1,2,3, Abdullaeva L.М.1, Kurbatova O.V.1, Tsvetkova V.S.1
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Affiliations:
- National Medical Research Center for Children’s Health
- I. Sechenov First Moscow State Medical University (Sechenov University)
- Central State Medical Academy of Department of Presidential Affairs
- Issue: Vol 26, No 3 (2023)
- Pages: 381-388
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/253417
- DOI: https://doi.org/10.46235/1028-7221-10044-COM
- ID: 253417
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Abstract
Myeloid-derived suppressor cells (MDSCs) play an important role in regulation of immune response. An increase in their number in adult patients with autoimmune diseases has been reported. G-MDSCs, M-MDSCs, and MDSCs(M-G-) at different stages of autoimmune disease may both activate T cell proliferation, leading to disease progression, or inhibit it, thus promoting Treg differentiation. Arginase-1 (Arg- 1) is an enzyme in MDSCs that reduces the concentration of arginine required for T lymphocyte proliferation. Our aim was to evaluate the content of MDSCs populations and functional activity of MDSCs in children with autoimmune diseases. 75 children with inflammatory bowel diseases (IBD), 60 children with multiple sclerosis (MS), 69 children with psoriasis (PS), 62 healthy age-matched children were included into the study. The content of MDSCs ((CD3, CD19, CD56, HLA-DR)-, CD11b+ and CD33+), subpopulations of MDSCs (M-MDSCs, G-MDSCs expressing CD14 and CD15), assessment of Arg-1 activity were performed by flow cytometry techniques. The content of MDSCs in patients with IBD, MS and PS was significantly higher than in the comparison group and depended on the state of exacerbation/remission. In exacerbation and remission of IBD, MS and PS, a significant increase of MDSCs was revealed when compared with healthy children; the highest values were found in children in exacerbation of MS (Me-3.5 (2.5-5.6) % MNC against Me-1.6 (0.9-2.5) % MNC, p < 0.001). In patients with MS, the content of G-MDSC, M-MDSC was significantly higher, and MDSC(M-G-) was lower than in healthy children. An increase in absolute amounts of G-MDSCs was shown in MS exacerbation compared to the disease remission state (p = 0.022). For patients with IBD, a significant increase in percentage of MDSCs and M-MDSCs (p = 0.014 and p = 0.045, respectively) was obtained in exacerbation of the disease relative to remission state. In patients with IBD, MS, and PS, a significant increase in Arg-1 activity in MDSCs was found, with a decreased number of MDSCs in patients in remission compared to exacerbation phase of the disease. In children with autoimmune diseases, an increase in the MDSC populations was found. The activity of arginase-1 in MDSCs is increased in remission, along with a decrease in their numbers.
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##article.viewOnOriginalSite##About the authors
Tatiana V. Radygina
National Medical Research Center for Children’s Health
Author for correspondence.
Email: tvradigina@mail.ru
ORCID iD: 0000-0003-4704-6885
Ph.D. (Medicine), Senior Research Associate, Laboratory of Experimental Immunology and Virology
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991Daria G. Kuptsova
National Medical Research Center for Children’s Health
Email: dg.kuptsova@gmail.com
ORCID iD: 0000-0001-7771-3314
Junior Researcher, Laboratory of Experimental Immunology and Virology
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991Svetlana V. Petrichuk
National Medical Research Center for Children’s Health
Email: cito@list.ru
ORCID iD: 0000-0003-0896-6996
PhD, MD (Biology), Professor, Chief Scientist, Laboratory of Experimental Immunology and Virology
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991Alexander S. Potapov
National Medical Research Center for Children’s Health; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: potapov@nczd.ru
ORCID iD: 0000-0003-4905-2373
PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Scientific Foundations of Pediatric Gastroenterology and Hepatology, Head of the Center for Inflammatory Bowel Diseases in Children, Head of Gastroenterology Department with Hepatology Group, National Medical Research Center for Children’s Health, Professor, Department of Pediatrics and Pediatric Rheumatology
Russian Federation, 1/2, Lomonosovskiy Pr-t, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991Nikolay N. Murashkin
National Medical Research Center for Children’s Health; I. Sechenov First Moscow State Medical University (Sechenov University); Central State Medical Academy of Department of Presidential Affairs
Email: m_nn2001@mail.ru
ORCID iD: 0000-0003-2252-8570
PhD, MD (Medicine), Professor, Head, Research Institute of Pediatric Dermatology, Dermatology Department with Laser Surgery Unit and Children’s Skin Pathology Laboratory, Professor, Department of Dermatovenereology and Cosmetology, Professor, Department of Pediatrics and Pediatric Rheumatology
Russian Federation, 1/2, Lomonosovskiy Pr-t, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991; 19/1A, Marshal Tymoshenko st., Moscow, 19991Luizat М. Abdullaeva
National Medical Research Center for Children’s Health
Email: instorm@inbox.ru
ORCID iD: 0000-0003-1574-2050
Junior Research assistant, Laboratory of rare hereditary diseases in children of the medical genetic center, neurologist of the Department of Psychoneurology and Psychosomatic Pathology
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991Olga V. Kurbatova
National Medical Research Center for Children’s Health
Email: putintseva@mail.ru
ORCID iD: 0000-0002-9213-5281
PhD (Medicine), Senior Research Associate, Head, Laboratory of Experimental Immunology and Virology
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991Valeriya S. Tsvetkova
National Medical Research Center for Children’s Health
Email: tsvetkova.valerie@gmail.com
ORCID iD: 0000-0002-8162-2957
PhD (Medicine), Research Associate, Gastroenterologist, Gastroenterology Department with Hepatology Group
Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991References
- Calahorra L., Camacho-Toledano C., Serrano-Regal M.P., Ortega M.C., Clemente D. Regulatory cells in multiple sclerosis: from blood to brain. Biomedicines, 2022, Vol. 10, no. 2, 335. doi: 10.3390/biomedicines10020335.
- Chen C., Tan L., Zhu W., Lei L., Kuang Y., Liu P., Li J., Chen X., Peng C. Targeting myeloid-derived suppressor cells is a novel strategy for anti-psoriasis therapy. Mediators Inflamm., 2020, Vol. 2020, 8567320. doi: 10.1155/2020/8567320.
- Gabrilovich D.I., Nagaraj S. Myeloid- derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol., 2009, no. 9, pp. 162-174.
- Goedegebuure P., Mitchem J. Myeloid-derived suppressor cells:general characteristics and relevance to clinical management of pancreatic cancer. Curr. Cancer Drug Targets, 2011, no. 11, pp. 734-751.
- Iacobaeus E., Douagi I., Jitschin R., Marcusson-Ståhl M., Andrén A.T., Gavin C., Lefsihane K., Davies L.C., Mougiakakos D., Kadri N., Le Blanc K. Phenotypic and functional alterations of myeloid-derived suppressor cells during the disease course of multiple sclerosis. Immunol. Cell Biol., 2018, no. 96, pp. 820-830.
- Ma Z., Zhen Y., Hu C., Yi H. Myeloid-derived suppressor cell-derived arginase-1 oppositely modulates IL-17A and IL-17F through the ESR/STAT3 pathway during colitis in mice. Front. Immunol., 2020, Vol. 11, 687. doi: 10.3389/fimmu.2020.00687.
- Melero-Jerez C., Fernández-Gómez B., Lebrón-Galán R., Ortega M.C., Sánchez-de Lara I., Ojalvo A.C., Clemente D., de Castro F. Myeloid-derived suppressor cells support remyelination in a murine model of multiple sclerosis by promoting oligodendrocyte precursor cell survival, proliferation, and differentiation. Glia, 2021, Vol. 69, no. 4, pp. 905-924.
- Millrud C.R., Bergenfelz C., Leandersson K. On the origin of myeloid-derived suppressor cells. Oncotarget, 2017, Vol. 8, pp. 3649-3665.
- Oka T., Sugaya M., Takahashietal N. CXCL17attenuates imiquimod-induced psoriasis-like skin inflammation by recruiting myeloid-derived suppressor cells and regulatory T cells. J. Immunol., 2017, Vol. 198, no. 10, pp. 3897-3908.
- Wu H., Zhen Y., Ma Z., Li H., Yu J, Xu Z.G., Wang X.Y., Yi H., Yanget Y.G. Arginase-1-dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus. Sci. Transl. Med., 2016, Vol. 8, 331ra40. doi: 10.1126/ scitranslmed.aae0482.
- Xu D., Li C., Xu Y., Huang M., Cui D., Xie J. Myeloid-derived suppressor cell: a crucial player in autoimmune diseases. Front. Immunol., 2022, Vol. 13, 1021612. doi: 10.3389/fimmu.2022.1021612.
- Xi Q., Li Y., Dai J., Chen W. High frequency of mononuclear myeloidderived suppressor cells is associated with exacerbation of inflammatory bowel disease. Immunol. Invest., 2015, no. 44, pp. 279-287.
- Zhang R., Ito S., Nishio N., Cheng Z., Suzuki H., Isobe K.I. Dextran sulphate sodium increases splenic Gr1+CD11b+ cells which accelerate recovery from colitis following intravenous transplantation. Clin. Exp. Immunol., 2011, Vol. 164, no. 3, pp. 417-427.
- Zhao F., Gong W., Song J., Shen Z., Cui D. The paradoxical role of MDSCs in inflammatory bowel diseases: From bench to bedside. Front. Immunol., 2022, Vol. 13, 1021634. doi: 10.3389/fimmu.2022.1021634
- Zoso A., Mazza E., Bicciato S., Mandruzzato S., Bronte V., Serafini P., Inverardi L. Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via treg-cell expansion. Eur. J. Immunol., 2014, no. 44, pp. 3307-3319.